An Inverstigation To The Nucleophilic Addition Reaction Of Difluoroenoxysilanes To Thioisatins

Benzothiophenones are widely encountered in plenty of pharmaceuticals and bioactive molecules.So far,the synthesis methods of benzothiophenones are still limited.This thesis focuses on studying the nucleophilic addition reaction of thioisatins with difluoroenoxysilanes,which provides a new method for the synthesis of 3-difluoroalkyl substituted 3-hydroxyl benzothiophenones with structural diversity.It also provides technical support for the research of pharmaceutically active moleculars with benzothiophenones and fluorinated drugs.The detailed research works are as following:1)A catalyst-free nucleophilic addition reaction of difluoroenoxysilanes to thioisatins is achieved,affording different products by changing the reaction solvent.The use of Me OH as the solvent enables the formation of 3-difluoroalkyl substituted 3-hydroxyl benzothiophenones as the major products,while seven-membered gem-difluoromethylene bridged benzo[d][1,3]oxathiepin-4（5H）-ones were obtained when H₂O is used as the solvent（likely via a sequential aldol-type/ring-opening/ring-closing reaction）.Moreover,mild reaction conditions,operational simplicity,and the gram-scale synthesis highlights the practicality of this method.2)A highly enantioselective Mukaiyama-aldol reaction of thioisatins with difluoroenoxysilanes is developed by using a chiral Cu（OTf）₂/Box complex as the catalyst,delivering a variety of difluoroalkylated 3-hydroxyl benzothiophenones in high to excellent yields and enantioselectivities.This is a new strategy for the asymmetric catalytic reaction of difluoroenoxysilanes,and successfully constructs a new class of chiral compounds,which provides convenience for the study of their pharmaceutical activity and structure-activity relationship.